Heat Shock Proteins in Benign Prostatic Hyperplasia and Prostate Cancer

Two out of three diseases of the prostate gland affect aging men worldwide. Benign prostatic hyperplasia (BPH) is a noncancerous enlargement affecting millions of men. Prostate cancer (PCa) in turn is the second leading cause of cancer death. The factors influencing the occurrence of BPH and PCa are different; however, in the course of these two diseases, the overexpression of heat shock proteins is observed. Heat shock proteins (HSPs), chaperone proteins, are known to be one of the main proteins playing a role in maintaining cell homeostasis. HSPs take part in the process of the proper folding of newly formed proteins, and participate in the renaturation of damaged proteins. In addition, they are involved in the transport of specific proteins to the appropriate cell organelles and directing damaged proteins to proteasomes or lysosomes. Their function is to protect the proteins against degradation factors that are produced during cellular stress. HSPs are also involved in modulating the immune response and the process of apoptosis. One well-known factor affecting HSPs is the androgen receptor (AR)—a main player involved in the development of BPH and the progression of prostate cancer. HSPs play a cytoprotective role and determine the survival of cancer cells. These chaperones are often upregulated in malignancies and play an indispensable role in tumor progression. Therefore, HSPs are considered as one of the therapeutic targets in anti-cancer therapies. In this review article, we discuss the role of different HSPs in prostate diseases, and their potential as therapeutic targets.

On the role of diagnosis of prostate diseases at the outpatient appointment of a therapist

Злокачественные заболевания остаются важной проблемой медицины, при этом ее решение зависит от эффективности выявления ранних стадий онкозаболеваний на амбулаторном этапе, включая терапевтическое звено оказания медицинской помощи. Существующие в настоящее время подходы к пропаганде основ здорового образа жизни преимущественно направлены лишь на профилактику поведенческих факторов риска: табакокурения, нерационального питания, недостаточной физической активности и пагубного употребления алкоголя. При этом, по оценкам экспертов, даже воздействие только на них позволит предотвратить по меньшей мере 40% случаев развития злокачественных новообразований. В России организована 3-уровневая система оказания медицинской помощи. Именно первый уровень оказания первичной медико-санитарной помощи и должен обеспечивать профилактическую направленность здравоохранения: грамотная диспансеризация способна обеспечить существенный, до 30%, вклад в снижение общей смертности населения, в том числе и смертности от злокачественных новообразований. Первым звеном диагностики онкологического заболевания являются терапевты, к которым пациенты обращаются с жалобами общего характера (утомляемость, субфебрилитет, боли в суставах, дизурия и т. д.). Наиболее актуальными задачами в работе терапевта являются своевременное обнаружение опухолевого заболевания и направление больного на лечение к онкологу. Статья рассматривает возможности скрининговых мероприятий с участием терапевтов, врачей общей практики, предлагает специально разработанные алгоритмы диагностики доброкачественных и злокачественных новообразований предстательной железы. Формирование навыков онкологической настороженности у врача первичного амбулаторного звена необходимо для раннего выявления и снижения частоты продвинутых стадий опухолей и более раннего начала специализированного лечения. Выявление симптоматики, подозрительной на злокачественные новообразования, с помощью алгоритмизированных подходов и последующая консультация пациента урологом или онкологом должны улучшить результаты лечения. Malignant diseases remain an important problem in medicine, while its solution depends on the effectiveness of detecting the early stages of cancer at the outpatient stage, including the therapeutic link in the provision of medical care. Currently existing approaches to the promotion of the foundations of a healthy lifestyle are mainly aimed only at the prevention of behavioral risk factors: tobacco smoking, unhealthy diet, insufficient physical activity and harmful use of alcohol. At the same time, according to experts, even exposure only to them will prevent at least 40% of cases of the development of malignant ovariances. A 3-tier system of medical care has been organized in Russia. It is the first level of primary health care that should ensure the prophylactic focus of health care: competent clinical examination is able to provide a significant, up to 30%, contribution to reducing the overall mortality of the population, including mortality from malignant neoplasms. The first stage in the diagnosis of oncological disease are therapists, to whom patients come with general complaints (fatigue, low-grade fever, joint pain, dysuria, etc.). The most urgent task in the work of a general practitioner is the timely detection of a tumor disease and referral of a patient for treatment to an oncologist. The article considers the possibilities of screening measures with the participation of therapists, general practitioners, and offers specially developed algorithms for the diagnosis of benign and malignant neoplasms of the prostate gland. The formation of oncological alertness skills in a primary outpatient care physician is necessary for early detection and reduction of the incidence of advanced stages of tumors and earlier initiation of specialized treatment. Identification of symptoms suspicious of malignant neoplasms using algorithmic approaches and subsequent consultation with the patient by a specialist urologist or oncologist should improve treatment outcomes.

Kinetic Studies of Newly Patented Aminoalkanol Derivatives with Potential Anticancer Activity as Competitive Inhibitors of Prostate Acid Phosphatase

Background: Acid phosphatase and its regulation are important objects of biological and clinical research and play an important role in the development and treatment of prostate and bone diseases. The newly patented aminoalkanol (4-[2-hydroxy-3-(propan-2-ylamino)propyl]-1,7-dimethyl-8,9-diphenyl-4-azatricyclo[5.2.1.02,6]dec-8-ene-3,5,10-trione hydrochloride) (I) and (4-[3-(dimethylamino)-2-hydroxypropyl]-1,7-dimethyl-8,9-diphenyl-4-azatricyclo[5.2.1.02,6]dec-8-ene-3,5,10-trione hydrochloride) (II) derivatives have potential anticancer activity, and their influence on enzymatic activity can significantly impact the therapeutic effects of acid phosphatase against many diseases. Therefore, in this study, we investigated the action of compounds (I) and (II) on acid phosphatase. Methods: Capillary electrophoresis was used to evaluate the inhibition of acid phosphatase. Lineweaver–Burk plots were constructed to compare the Km of this enzyme in the presence of inhibitors (I) or (II) with the Km in solutions without these inhibitors. Results: Compound (I) showed a stronger competitive inhibition against acid phosphatase, whereas derivative (II) showed a weaker competitive type of inhibition. The detailed kinetic studies of these compounds showed that their type and strength of inhibition as well as affinity depend on the kind of substituent occurring in the main chemical molecule. Conclusions: This study is of great importance because the disclosed inhibition of acid phosphatase by compounds (I) and (II) raises the question of whether these compounds could have any effect on the treatment possibilities of prostate diseases.

Estrogen Receptor β Participates in Alternariol-Induced Oxidative Stress in Normal Prostate Epithelial Cells

Alternaria toxins are considered as emerging mycotoxins, however their toxicity has not been fully evaluated in humans. Alternariol (AOH), the most prevalent Alternaria mycotoxin, was previously reported to be genotoxic and to affect hormonal balance in cells; however, its direct molecular mechanism is not known. The imbalance in androgen/estrogen ratio as well as chronic inflammation are postulated as factors in prostate diseases. The environmental agents affecting the hormonal balance might participate in prostate carcinogenesis. Thus, this study evaluated the effect of two doses of AOH on prostate epithelial cells. We observed that AOH in a dose of 10 µM induces oxidative stress, DNA damage and cell cycle arrest and that this effect is partially mediated by estrogen receptor β (ERβ) whereas the lower tested dose of AOH (0.1 µM) induces only oxidative stress in cells. The modulation of nuclear erythroid-related factor 2 (Nrf2) was observed in response to the higher dose of AOH. The use of selective estrogen receptor β (ERβ) inhibitor PHTPP revealed that AOH-induced oxidative stress in both tested doses is partially dependent on activation of ERβ, but lack of its activation did not protect cells against AOH-induced ROS production or DNA-damaging effect in case of higher dose of AOH (10 µM). Taken together, this is the first study reporting that AOH might affect basic processes in normal prostate epithelial cells associated with benign and malignant changes in prostate tissue.

A STUDY ON CORRELATION OF SERUM PROSTATE SPECIFIC ANTIGEN WITH CLINICAL AND PATHOLOGICAL VARIABLES IN PATIENTS OF PROSTATOMEGALY

Background: In clinical practice, biopsies are generally performed only when the results ofprostate specific antigen (PSA) test or digital rectal examination (DRE) are abnormal. This leads to misdiagnosis of most small prostatic cancers present in many older men. Patients with lower urinary tract infection (LUTS) who have serum PSA levels higher than 4ng/ml are primarily advised to undergo prostate biopsy to rule out cancer. However, PSA is organ specific not disease specific, so the presence of other prostate diseases such as benign prostatic hyperplasia (BPH) and prostatitis may influence its effectiveness for cancer detection. Hence, the PSA based prostate cancer detection is fraught with high false positive rate. Aim:To evaluate the utility of PSA assay as a method of investigation in diagnosis of prostatic lesion. Objectives: The use of Serum PSA levels for the early detection of prostate cancer and evaluate its role with other modalities for diagnosis of prostate cancer and to diagnose different diseases of prostate, i.e. prostatitis, BPH in prostatomegaly, and its correlation with Serum PSA levels. Materials and Methods: This prospective descriptive study was conducted in Index Medical College, Hospital & Research Centre, Indore, M.P,India in the period of August 2019 to July 2021. The patients were selected from the outdoor Department of General Surgery. Results: A total of 80 male patients presenting with LUTS were included. Their mean age was 68.66 years. The majority i.e. 41 of the study group were in the age group of 61-70 years. 42 of patients had Serum PSA < 4ng/ml. Biopsy proven adenocarcinoma cases 34% of the cases are in the age group of 61-70 years. Out of the biopsy proven adenocarcinoma cases, DRE was suspicious of malignancy in 89%. Conclusion: Serum PSA levels have a significant correlation with the age group, with the increase in age there is rise in Serum PSA levels. Transabdominal ultrasound, DRE and Serum PSA has high sensitivity in diagnosis of prostatomegaly but it was found that none of the screening tool has got much efficacy in differentiating carcinoma prostate from benign hypertrophy, but the combination of DRE and Serum total PSA or DRE, Serum total PSA and ultrasound abdomen showed higher efficacy in diagnosis of carcinoma prostate. Increase in Serum PSA is directly related to carcinoma, but there is no absolute cut-off for Serum PSAfor diagnosis of carcinoma. Key-Words: Prostate specific antigen, Prostatomegaly, Benign Prostatic Hypertrophy, Digital Rectal Examination, International Prostate Severity Score, Carcinoma Prostate.

Bladder neck sclerosis: alternative methods of treatment and prospects for their development

Introduction. Bladder neck sclerosis (BNS) is a widespread complication of the surgical treatment of prostate diseases. Nevertheless, the etiology and pathogenesis of BNC development are not well understood, the frequency and degree of iatrogenic BNS varies depending on what treatment took place before its appearance. Treatment options for BNS can vary from simple dilatation to complex surgical interventions. Clinical variants of BNS, as well as their treatment options, vary in complexity, from simple short annular contractures to obliterating stenosis, which requires a significant expansion of surgical treatment volume. The purpose of this study – is to assess the effectiveness of modern and alternative methods of prevention and treatment of BNS based on the analysis of published studies. Materials and methods. The search and analysis of publications in the databases PubMed, Scopus, Cochrane Library, elibrary, according to the keywords, «bladder neck sclerosis», «benign prostatic hyperplasia», «bladder neck contracture», «bladder neck stenosis», «balloon dilatation», «treatment». As a result, 46 publications were selected and included in this review. Results and discussion. In this review, we highlighted the routine and alternative methods of BNS treatment. Currently, there are quite modern methods for treating prostate diseases (using robotic techniques, electrosurgical resections, and enucleations, laser enucleations, etc.), which are often complicated by secondary BNS. Nowadays, there are a lot of routine and alternative methods of treatment of secondary BNS in the urologist’s armamentarium. Routine methods include TUR and incision of the bladder neck using electric and laser energy, alternative methods include balloon dilatation, installation of a urethral stent, instillation (or intraoperative injection) of the bladder with cytostatics, hormonal drugs, derivatives of hyaluronic acid, and biomedical cell products. Conclusions. According to the literature from the listed alternative treatment methods for BNS, balloon dilatation is the most promising one. Based on the results of the literature analysis, we concluded that the use of balloon dilatation as a method of primary (least invasive) treatment and prevention of the occurrence of BNS is advisable.

Clinical use of cytomedin in patients with prostate diseases

Introduction. The use of extracts of the prostate of animals is one of the main directions in the treatment of patients with diseases of the prostate. Most studies describe the experience of using these drugs in a small number of patients for a limited time period. The aim of this work was to summarize the long-term experience of using drugs of the cytomedin group in the treatment of a large number of patients with chronic prostatitis (CP) and benign prostatic hyperplasia (BPH). Materials and methods. Cytomedins were used in 487 patients with CP / BPH from January 2015 to December 2018. Indications: rehabilitation of patients after pancreatic biopsy (63 patients, 13%), cystoscopy and other endoscopic surgical interventions (189 patients, 39%), as well as conservative therapy of chronic inflammation associated with BPH (235 patients, 48%). If an infectious-inflammatory process was suspected, the following scheme was used: Vitaprost Plus 1 candle 1 time per day for 20 days, in the presence of irritative complaints, Vitaprost Forte was used 1 candle 1 time per day for 20 days, in other cases Vitaprost was prescribed 1 candle 1 time per day for 20 days ... The second component of the complex treatment was the use of the Vitaprost tablet form for 20 days, 1 ton 2 times a day. Before and after the appointment of therapy, the quality of life was monitored according to the data of the visual analogue scale (VAS), ultrasound examination of the pancreas (ultrasound) and laboratory parameters. The results of therapy were assessed as successful with an improvement in the quality of life, a decrease in the level of leukocytes, and a decrease in the volume of the pancreas by more than 10% from the initial level. Results. The total efficacy of cytomedin therapy was 39%. The greatest effectiveness of therapy was with the initial VAS less than 60 points out of 100; with more severe pain syndrome, the effectiveness was statistically significantly reduced to 32%. The initial detection of an inflammatory component with an increase in the level of leukocytes in laboratory tests statistically significantly increased the effectiveness of therapy 48 versus 24%. Cytomedin therapy was equally effective regardless of the prostate volume (36% versus 42% versus 38%, p> 0.05). A survey was conducted in 102 patients after Vitaprost-Forte / Vitaprost therapy, the results of which revealed a decrease in the I-PSS score from 18 ± 6.4 points to 12 ± 4 points (p> 0.05), in the group with combination therapy with alpha adrenergic blockers – 8 ± 3.2 points, p <0.05. A control examination of 51 patients with the development of erectile dysfunction against the background of chronic intake of 5-ARI showed that the cancellation of 5-ARI inhibitors followed by the appointment of Vitaprost in the form of suppositories and tablets led to an increase in the IIEF-5 indicator by 5 points, the average indicator during the control examination was 23 ± 4.2 points (p> 0.05) versus 18 ± 3.4 points before treatment. Conclusions. the following prognostic criteria for the effectiveness of cytomedin therapy were determined: the level of the visual analogue scale is less than 60 out of 100 and the presence of a confirmed inflammatory component according to laboratory tests.

Combined Effects of Different Endocrine-Disrupting Chemicals (EDCs) on Prostate Gland

Endocrine-disrupting chemicals (EDCs) belong to a heterogeneous class of environmental pollutants widely diffused in different aquatic and terrestrial habitats. This implies that humans and animals are continuously exposed to EDCs from different matrices and sources. Moreover, pollution derived from anthropic and industrial activities leads to combined exposure to substances with multiple mechanisms of action on the endocrine system and correlated cell and tissue targets. For this reason, specific organs, such as the prostate gland, which physiologically are under the control of hormones like androgens and estrogens, are particularly sensitive to EDC stimulation. It is now well known that an imbalance in hormonal regulation can cause the onset of various prostate diseases, from benign prostate hyperplasia to prostate cancer. In this review, starting with the description of normal prostate gland anatomy and embryology, we summarize recent studies reporting on how the multiple and simultaneous exposure to estrogenic and anti-androgenic compounds belonging to EDCs are responsible for an increase in prostate disease incidence in the human population.

The Molecular Aspect of Nephrolithiasis Development

Urolithiasis is the third most common urological disease after urinary tract infections and prostate diseases, and it is characterised by an occurrence rate of about 15%, which continues to rise. The increase in the incidence of kidney stones observed in recent decades, is most likely caused by modifications in dietary habits (high content of protein, sodium and sugar diet) and lifestyle (reduced physical activity) in all industrialised countries. Moreover, men are more likely than women to be diagnosed with kidney stones. A growing body of evidence suggests that inflammation, oxidant–antioxidant imbalance, angiogenesis, purine metabolism and urea cycle disorders may play a crucial role in nephrolithiasis development. Patients with urolithiasis were characterised by an increased level of reactive oxygen species (ROS), the products of lipid peroxidation, proinflammatory cytokines as well as proangiogenic factors, compared to controls. Furthermore, it has been shown that deficiency and disorders of enzymes involved in purine metabolism and the urea cycle might be causes of deposit formation. ROS generation suggests that the course of kidney stones might be additionally potentiated by inflammation, purine metabolism and the urea cycle. On the other hand, ROS overproduction may induce activation of angiogenesis, and thus, allows deposit aggregation.